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Finding a better factory

A newly characterized yeast strain has the potential to improve the efficiency and economics of therapeutic protein production

Although many diseases can be treated with protein-based drugs, producing them affordably in large quantities remains challenging. Yeast can be genetically engineered to produce proteins from other eukaryotic organisms with reasonable fidelity, but the species used in laboratory settings are too inefficient for drug manufacture.

‘Methylotrophic’ yeasts, which can be easily cultivated in methanol-containing medium, offer a promising alternative. Researchers led by Sutipa Tanapongpipat of Thailand’s National Science and Technology Development Agency have now characterized the protein-production performance of a methylotrophic strain, Pichia thermomethanolica, isolated from soil samples from southern Thailand.

They engineered P. thermomethanolica to produce two different fungal enzymes, phytase and xylanase, and achieved production at temperatures ranging from 30–40 °C, giving scientists greater flexibility for culture conditions than is possible with conventional, temperature-sensitive yeast.

To function properly, many secreted proteins must undergo a process called glycosylation, in which they are tagged with sugar molecules by specialized enzymes. Tanapongpipat and colleagues determined that foreign proteins expressed in P. thermomethanolica undergo extensive glycosylation, and that these modifications could be altered by modifying culture conditions.

The researchers hope to exploit this yeast’s reduced temperature-sensitivity as a means to achieve lower-cost manufacture of functional therapeutic proteins. They are also looking into ways to boost the productivity of this promising species.